Persistent developmental stuttering (PDS) affects 1% of the adult population with a lifetime incidence of approximately 4%. The major aim of this application is to identify quantitative neuroanatomical endophenotypes associated with PDS. Endophenotypes are susceptibility-related phenotypes, even in individuals who do not overtly display symptoms of a disorder. Linkage analysis of stuttering can use endophenotypes to understand the genes implicated, an approach now taken in many complex genetic disorders. Knowing the genes predisposing susceptibility to PDS will aid in the understanding and treatment of the disorder. Understanding the nature and cause of PDS is one of the missions of the NIDCD, Voice, Speech, and Language Program. The proposed work also falls in line with other stated goals of the NIDCD, such as understanding the genetic bases of language disorders in childhood, a natural future extension of this work. There are two specific aims in the application which will complement the solid foundation of behavioral and neurophysiologic traits of adults who stutter (AWS) with quantitative neuroanatomical traits. This is based on the reasoning that: PDS is a complex genetic disorder, endophenotypes are now routinely used to study such disorders, brain morphology has several highly heritable features, and preliminary studies suggest PDS is associated with subtle cortical folding abnormalities. Specific Aim 1 of this project will characterize the cortical thickness (Aim 1A) and regional gyrification profiles (Aim 1B) of AWS. This will be done by rater-indendent means using automated image analysis tools. Additionally, diffusion-weighted imaging will be employed in Specific Aim 2 to assess the connectional architecture of the brain, through tract-based comparisons (Aim 2A) and a tract-tracing approach to the corpus callosum (Aim 2B). The studies of Aim 2A are appropriate because studies of AWS have described focused abnormalities in the left hemisphere speech system with diffusion tensor imaging. The proposed work will attempt to first replicate, and then extend, this potential endophenotype. Additionally, tractography methods will be used to evaluate hypothesized aberrant connections within the corpus callosum, a highly heritable structure. These studies will provide a rater-independent, cost-effective, minimally-invasive tool for dissecting the genes involved in susceptibility to the disorder. RELEVANCE: Developmental stuttering is a speech disorder affecting both children and adults. It is known to have a genetic basis, but the genes involved are still largely unknown. Understanding the genetic basis of the disorder will help improve diagnostic approaches and treatment strategies. [unreadable] [unreadable] [unreadable]